The therapeutic window represents the range of drug dosages by which a disease can be treated efficiently and safely. It ranges from the dosage at which a noticeable therapeutic effect is seen to that at which the therapeutic benefit is neutralized by adverse effects.
The majority of anticancer drugs have a narrow therapeutic window. In addition it is often a tiny fraction of an administered dose that reaches the site to be treated. Upon systemic administration by oral ingestion or intravascular injection, the medication is distributed throughout the body via the circulation resulting in the entire body being affected. Ideally, the medication should be directed exclusively to a desired body site such as an organ or tissue in need of treatment. Such targeted administration would avoid harming the rest of the body. This kind of administration seeks to direct the medication to tissues of interest while avoiding substantial amounts thereof reaching tissues that do not require treatment.
An example of drugs which need to be directed to a specific body site is the anti-cancer drug doxorubicin. It is generally accepted that the therapeutic potential of doxorubicin could be significantly improved by targeted drug delivery since its dangerous side effects thereby could be avoided or at least substantially reduced. The most dangerous side effect of doxorubicin is damage to the heart. When the cumulative dose of doxorubicin reaches 550 mg/m2, the risk of developing cardiac side effects increases dramatically. Doxorubicin cardiotoxicity is characterized by a dose-dependent decline in mitochondrial oxidative phosphorylation. Reactive oxygen species generated by the interaction of doxorubicin with iron can damage myocytes causing myofibrillar loss and cytoplasmic vacuolization. Excessive damage of this kind may result in the death of the patient. It is therefore desirable to keep the cardiac concentration of doxorubicin as low as possible.
Liver cancer is one of a number of malignancies in which administration of doxorubicin is indicated. More specifically, liver cancer can be treated by targeted (or local) administration in a procedure known as transarterial chemoembolization. In this procedure doxorubicin is administered through a catheter directly to artery(ies) feeding the diseased portion of the liver while arteries supplying portions of the liver not affected by the disease are blocked by, for instance, gelatin sponge.
Isolated liver perfusion is one approach for targeted delivery of drugs to the liver. It comprises a surgical procedure during which the circulation of blood to the liver is separated from general circulation and separately perfused with blood. After separation the drug is injected into the blood by which the liver is being perfused, allowing a higher concentration of chemoterapeutical agent(s) to be used than with systemic administration. This invasive procedure is however technically complicated and not safe.
Many pharmacologically active agents such as the aforementioned anti-cancer drugs are week bases in that they comprise one or more amino groups. For this reason they form salts with strong and weak acids, and are usually administered in salt form. The solubility of their common pharmaceutically acceptable salts, in particular their hydrochlorides, hydrobromides, phosphates, sulfates, lactates, tartrates, etc. in aqueous body fluid is usually higher than the solubility of the free base. Therefore aqueous solutions of such salts are used for intravenous infusion rather than an aqueous solution of the respective base.
For administration to the liver of a person or animal anti-cancer drugs of this kind are provided in a cationic amphiphilic form (in the form of a salt with a pharmaceutically acceptable acid). This manner of administration is applied but not limited to anti-cancer drugs such as, for instance, anthracyclines (doxorubicin, epirubicin, daunorubicin, idarubicin, mitoxantrone), vinca alkaloids (vinblastine, vincristine, vinorelbine), amsacrine, topotecan and irinotecan. If a pharmacologically active agent comprises more than one amino group two or more of them may be protonated and form salts with an acid.
Cationic amphiphilic drugs (CAD) of the aforementioned kind react with amphiphilic anionic surfactants, such as alkyl sulfates or alkane sulfonates, to form water insoluble complexes.

While still meeting the definition of a salt of an organic base with an organic or inorganic acid, the water insoluble complexes are to some extent additionally linked by non-covalent forces.